1. Field of the Invention
The present invention relates to the chromatographic fractionation of plasma proteins, and, more especially, to the fractionation of plasma by means of ion exchangers to obtain high purity albumin.
2. Description of the Prior Art
The technique most widely used on an industrial level to separate the principal components of plasma, albumin and immunoglobulins, is the Cohn method, the principle of which being based upon the selective precipitation of proteins with the aid of aqueous alcoholic solutions. The processes for precipitation are not perfectly selective and are particularly denaturating; they entail lengthy processing that is labor and cost intensive and the provision of sterile and apyrogenic products is an especially delicate operation.
With the introduction of the ion exchange materials, novel methods have been proposed to continuously separate the proteins from their mixtures in fixed bed columns. These processes are more economical and make it possible to obtain proteins of higher purity, in better yields. However, their application on a large scale in the biological industry is still fraught with a number of difficulties.
Processes for the isolation of the albumin in blood plasma by contact with polysaccharide ion exchangers are described in French Patent No. 2,327,256, and in U.S. Pat. Nos. 4,228,154 and 4,136,094. These processes involve complex preliminary treatments to eliminate the major portion of the impurities, in particular the lipoproteins, and in certain cases the .gamma.-globulins and/or require a subsequent purification of the albumin using molecular sieves to obtain a degree of purity in excess of 98%. These supplemental treatments are difficult to apply industrially and are expensive. Moreover, productivity is low and ill suited for the treatment of large volumes of plasma, the need for which is accentuated by the constantly increasing worldwide demand for such proteins.
The inorganic or mineral supports, in contrast to the polysaccharides, have excellent physical/mechanical properties permitting high degree of filtration, but the adsorption sites of which, as a function of pH and available ionic strength, may result in significant decreases in protein yield.
Processes for the separation of proteins by chromatography on mineral ion exchange supports are described in detail in, for example, French Pat. Nos. 2,321,932, 2,359,634 and 2,464,967. The combination of the ion exchangers described may result, in the case of plasma fractionation, in inadequate yields for the degrees of purity required for therapeutic applications and does not yield high purity albumins regardless of the plasma to be fractionated.